Tag Archives: C. difficile treatment clinical trial

Surotomycin Failed To Show Benefit Over Vancomycin In a Pivotal Phase 3 Trial To Treat C. difficile Infections

A similar proportion of patients with Clostridium difficile infection showed clinical response at the end of treatment with surotomycin vs. vancomycin in a pivotal phase 3 trial.

However, surotomycin did not demonstrate superiority for key secondary endpoints including sustained clinical response and clinical response over time, and therefore failed to show benefit over vancomycin.

 

As published :  https://www.healio.com/gastroenterology/infection/news/online/%7B3531418d-42aa-4092-a9f2-55ba2ce6dcda%7D/surotomycin-meets-non-inferiority-endpoint-fails-to-show-benefit-over-vancomycin-in-c-difficile

This follows previously reported results of a parallel phase 3 trial in which surotomycin failed to meet non-inferiority criteria relative to vancomycin for primary and key secondary endpoints.

“Surotomycin has a narrow spectrum of activity, demonstrating low resistance rates and rapid activity against C. difficile with similar dose- and time-dependent pharmacodynamics to vancomycin in resolving CDI in a hamster model,” Sahil Khanna, MBBS, of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., told Healio Gastroenterology and Liver Disease.

In this second phase 3 trial, “surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at end of treatment. It was similar to vancomycin for sustained clinical cure.”

In this double-blind, international multicenter trial, Khanna and colleagues randomly assigned 285 patients with confirmed CDI to receive 250 mg oral surotomycin twice daily alternating with placebo twice daily, and 292 to receive 125 mg oral vancomycin four times daily for 10 days.

At the end of treatment, clinical response with surotomycin (83.4%) was non-inferior to vancomycin (82.1%), with a difference of 1.4% (95% CI, 4.9-7.6).

Through 30 to 40 days of follow-up, clinical response over time was not superior to surotomycin, nor was sustained clinical response (63.3% vs. 59%; difference, 4.3%; 95% CI, 3.6-12.2).

Both treatments were generally well tolerated, with typical treatment-emergent adverse events occurring in 52.4% of patients treated with surotomycin and 60.1% of those treated with vancomycin.

“Interestingly, in the hypervirulent strain of CDI, recurrence rate was lower for surotomycin vs. vancomycin,” Khanna said, though he and colleagues noted in the study manuscript that “this finding is nominal due to a lack of multiplicity control.”

Based on the results of these trials, the surotomycin development program has been discontinued, but “the non-inferiority of surotomycin to vancomycin observed in the current trial is in contrast with the parallel trial,” investigators wrote. – by Adam Leitenberger

Disclosures: This study was funded by Merck. Khanna reports he has served as an advisor to Summit Pharmaceuticals and serves as a consultant to Rebiotix and Assembly Biosciences. Please see the full study for a list of all other researchers’ relevant financial disclosures.

SOURECE:  https://www.healio.com/gastroenterology/infection/news/online/%7B3531418d-42aa-4092-a9f2-55ba2ce6dcda%7D/surotomycin-meets-non-inferiority-endpoint-fails-to-show-benefit-over-vancomycin-in-c-difficile

Summit Announces Positive Data From Phase 2 C. difficile Clinical Trial Supporting Ridinilazole To Treat C. diffiicle Infection

SUMMIT ANNOUNCES POSITIVE TOP-LINE DATA FROM AN EXPLORATORY PHASE 2 CLINICAL TRIAL SUPPORTING RIDINILAZOLE AS A HIGHLY SELECTIVE ANTIBIOTIC FOR THE TREATMENT OF CDI

  • Ridinilazole treatment more preserving of gut microbiome than fidaxomicin

 * Listen In on September 26th 10aPT/1pET www.cdiffradio.com   live broadcast with our guests from Summit Therapeutics.

 

 

Oxford, UK, 5 September 2017Summit Therapeutics plc (NASDAQ: SMMT, AIM: SUMM), the drug discovery and development company advancing therapies for Duchenne muscular dystrophy and Clostridium difficile infection (‘CDI’), today announces positive top-line data from an exploratory Phase 2 clinical trial that support ridinilazole as a highly selective and potent antibiotic product candidate for the treatment of CDI. In the Phase 2 clinical trial, ridinilazole preserved the gut microbiome of CDI patients to a greater extent than the marketed narrow-spectrum antibiotic, fidaxomicin. During the trial’s ten-day treatment period, ridinilazole treatment had markedly less impact on the gut microbiome of trial patients by measures of overall diversity and changes in key bacterial families, when compared to those trial patients dosed with fidaxomicin.

 

In the trial, ridinilazole and fidaxomicin both reduced the abundance of C. difficile. However, fidaxomicin-treated patients had reduced abundancy of other bacterial families associated with microbiome health. For a number of these bacterial families, the difference between the two treatments was statistically significant. Another measure of microbiome health is alpha diversity as measured by the Simpson’s Diversity Index. There was a greater reduction in alpha-diversity during fidaxomicin treatment compared with ridinilazole-treated patients. These measures were a key secondary endpoint of the clinical trial and provide additional evidence of ridinilazole’s precision in killing C. difficile while preserving the gut microbiome. The primary endpoint of the trial was safety, as measured by the number of treatment emergent adverse events and serious adverse events. During the trial, no new or unexpected safety signals were identified and ridinilazole was well-tolerated.

 

“We increasingly recognise the importance of a healthy and diverse gut microbiome for protection against recurrent CDI, which is a major challenge in the management of the disease. These latest clinical findings show ridinilazole better preserved the microbiome of CDI patients than fidaxomicin, the narrowest spectrum antibiotic currently available for CDI,” commented Professor Mark Wilcox, Consultant Microbiologist & Head of Microbiology Research & Development at the Leeds Teaching Hospitals NHS Trust, Professor of Medical Microbiology at the University of Leeds, and Public Health England’s Lead on C. difficile in England. “Further, these microbiome data are very supportive of ridinilazole’s profile as a highly selective antibiotic with the potential to achieve a meaningful improvement in clinical outcomes for CDI patients.”

 

The exploratory open-label Phase 2 clinical trial enrolled 27 patients aged between 18 and 90 years at trial sites in the US, the UK and the Czech Republic. Patients were randomly assigned to receive either ridinilazole (200mg, twice a day) or fidaxomicin (200mg, twice a day) for ten days. The trial population was unbalanced with more patients randomised to ridinilazole at higher risk of poorer clinical outcomes as measured by ATLAS score, and also with predisposing factors for recurrent CDI.

 

A secondary endpoint of sustained clinical response (‘SCR’), defined as clinical cure at the end of treatment and no recurrence of CDI within the next 30 days, was achieved in seven of 14 ridinilazole treated patients and six of 13 fidaxomicin treated patients. The trial was not designed for efficacy comparisons due to the small number of patients.

 

Dr David Roblin, Chief Medical and Operating Officer of Summit added, “Ridinilazole is a precision antibiotic that is designed to selectively target C. difficile while being highly preserving of the gut microbiome that plays a crucial role in naturally protecting against recurrent CDI. Ridinilazole has now provided evidence of its high selectivity in two complementary clinical trials. The data from our earlier Phase 2 trial showed a greater microbiome preservation of ridinilazole-treated patients compared with the current standard of care, vancomycin, which led to achieving statistical superiority in sustained clinical response. We believe ridinilazole has the potential to become a front-line therapy for CDI and look forward to initiating Phase 3 clinical trials in the first half of 2018.”

 

More detailed findings from this trial are expected to be presented at an upcoming international infectious disease conference. The results build on positive data from a Phase 2 proof of concept trial of ridinilazole that were published in The Lancet Infectious Diseases in April 2017. Ridinilazole is currently being prepared for Phase 3 clinical trials that are planned to commence in the first half of 2018.

 

SOURCE:  www.summitplc.com

C. diff. In the News – New Antibiotic Could Treat C. diff. In Time

Access article/video in its entirety by clicking on the following link:

http://www.bbc.com/news/uk-scotland-34106754

New antibiotic could transform C. diff treatment

Clinical trials have begun of a treatment that could fight outbreaks of the bacterial infection Clostridium difficile.

Scientists at Strathclyde University (Scotland), who developed the antibiotic, say it is the first of a new class of drug that could transform the treatment of potentially fatal diseases.

 

 

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.

Recurrent C. difficile Infection; Seres Health Plans To Use Funding To Advance SER-109, Into Phase 3 Clinical Trials

NewsSpeaker

Seres Health, Cambridge, MA based, a contender in the haute field of microbiome therapeutics, just hauled in a $48 million Series C round.

The startup’s developing biologics that target recurrent C.difficile infections.

 

 

The company plans to use the funding to advance its lead candidate, SER-109, into Phase 3 clinical trials. If approved, Seres’ therapeutic line – called Ecobiotic – will be the first oral microbiome-related therapeutic that receives the regulatory go-ahead.

The Ecobiotic system works by “augmenting the biology of the microbiome,” Seres said. In September it released results from its earlier SER-109 trial, in which 29 of the study’s 30 patients were completely cured of their C. dificile infections over the course of 8 weeks. The patients received oral doses of Seres’ microbiome “spores” – that is, precursors to “good” gut bacteria that mature into disease-fighting agents. They’ve been isolated from human fecal matter, then delivered in pill-form to the patient – a promising approach given the growing bacterial resistance to antibiotics.

In addition to treating clostridium-related disease, Seres’ pipeline pursues other as-yet-unnamed indications in the metabolic, inflammatory and infectious disease spaces.

Seres Health was launched in 2012 by Flagship Ventures. This past June, it teamed up with Mayo Clinic  for an exclusive research partnership.

 

 

*Please note – The C Diff Foundation does not endorse this product or any product and this posting is strictly for informational purposes only.